Bansal N, David G, Farias E, Waxman S
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
New York University School of Medicine, New York, NY, United States.
Adv Cancer Res. 2016;130:113-35. doi: 10.1016/bs.acr.2016.01.006. Epub 2016 Mar 2.
Revolutionizing treatment strategies is an urgent clinical need in the fight against cancer. Recently the scientific community has recognized chromatin-associated proteins as promising therapeutic candidates. However, there is a need to develop more targeted epigenetic inhibitors with less toxicity. Sin3 family is one such target which consists of evolutionary conserved proteins with two paralogues Sin3A and Sin3B. Sin3A/B are global transcription regulators that provide a versatile platform for diverse chromatin-modifying activities. Sin3 proteins regulate key cellular functions that include cell cycle, proliferation, and differentiation, and have recently been implicated in cancer pathogenesis. In this chapter, we summarize the key concepts of Sin3 biology and elaborate the recent advancements in the role of Sin3 proteins in cancer with specific examples in multiple endocrine neoplasia type 2, pancreatic ductal adenocarcinoma, and triple negative breast cancer. Finally, a program to create an integrative approach for screening antitumor agents that target chromatin-associated factors like Sin3 is presented.
革新治疗策略是抗癌斗争中一项紧迫的临床需求。最近，科学界已将与染色质相关的蛋白质视为有前景的治疗候选物。然而，需要开发毒性更低的更具靶向性的表观遗传抑制剂。Sin3家族就是这样一个靶点，它由具有两个旁系同源物Sin3A和Sin3B的进化保守蛋白组成。Sin3A/B是全局转录调节因子，为多种染色质修饰活动提供了一个多功能平台。Sin3蛋白调节包括细胞周期、增殖和分化在内的关键细胞功能，并且最近已被证明与癌症发病机制有关。在本章中，我们总结了Sin3生物学的关键概念，并以多发性内分泌肿瘤2型、胰腺导管腺癌和三阴性乳腺癌中的具体例子详细阐述了Sin3蛋白在癌症中作用的最新进展。最后，提出了一个创建综合方法以筛选靶向Sin3等与染色质相关因子的抗肿瘤药物的方案。
